Kinetic Study of the Effect Some Novel Lipid Lowering Compounds on Creatine Kinase and 3-Hydroxy-3-Methy-Glutaryl-CoA Reductase Activities

Hyperlipidemia is one of the most important factors leading  to atherosclerosis and heart disease, therefore,  this study conducted to examine the effect of two newly synthesized compounds[3-(5-(ethylthio)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-2-(3-nitrophenyl)benzo[1-3-e] thiazin-4-one (I) and 5(4-dimethyl amino) benzylidene amino)-1,3,4-thiadiazole-2-thiol(II)] on the activities of creatine kinase(CK) and 3-hydroxy-3-methylglutaryl- CoA reductase (HMG-CoA redutase) in serum of hyperlipidemic patients in vitro study. Also to determine the type of inhibition of these compounds on the above enzymes which may be used as lipid lowering agents in future. The results revealed that compound I showed the best inhibition effect at 10-4 M concentration, while compound II showed the best inhibition effect at 10-5M concentration for both enzymes. The effect of compound I on CK activity was found to be noncompetitive inhibitor with Vmax values (1000 and 344.82)U/L respectively for the uninhibited and inhibited reactions and Km value (10)mmol/L while compound II was found to be competitive inhibitor with Vmax value (588.23)U/L and Km values (5.51 and 4)mmol/L respectively for the uninhibited and inhibited reactions. Compounds I and II were found to be competitive inhibitors on HMG-CoA reductase with Vmax value (0.020)U/L and Km values(0.339 and 0.125)mmol/L respectively for the uninhibited  and inhibited reactions for compound I and Vmax value (0.021) U/L and Km values(1.111 and 0.256)mmol/L respectively for the uninhibited and inhibited reactions for compound II. In conclusion the new compounds(I and II) showed different inhibitory effect on CK and HMG-CoA reductase activities that could be used in treatment of hyperlipidemia and related disease in future. Key words: lipid lowering compounds, CK and HMG-CoA reductase